Aminophenyl arsenic compound.



; STANCE OFFICE.

ALBxopngH. 0.. o1? DETROIT, MICHIGAN, AssIGNoR 'ro PARKE, DAVIS &

CQMPANY, on DETROIT, MICHIGAN, A CORPORATION 01 MICHIGAN.

AMINOPHENYL ARSENIO COMPOUND.

1.,119; 27e; R Drawing.

To it may 0mm.-

Be lt'knownthat' -I,-AnNOI;n H. C. Hnrr- MAN, a citizen'of the UnitedStates, residin thecity-of Detroit, county of Wayne, an

lStateof Michigan, have invented certain iof an amino group inamino-phenyl-arsencoming Within my. generic invention.

oxid, (which compound has been found very effective in a. test tubeagainst certain specific disease organisms, but extremely toxic t thecells of the animal host is replaced by a. carbethoxyl group, COoC H acom- .pound is obtained which isver'y much less organo-tropic than itsmother substance, {while its parasito-tropicor disease destroytingproperty is thereby much enhanced.

."Examples of new specific in oxid form are 1 the following:carbethoxy-para-aminocarbethoxyt-5-diamino phenyl-arsen oxid,

BN-GOOCdL It is presumably true that, founded upon my discoveries,substitutions may be made for otherhydrogensin the benzene ring, and

that other elements, such as sulfur, selenium or tellurium' will besubstituted for oxygen in the arsenic radical; such substitutions In theproduction of these products I first produced the correspondingpen'ta-valent carbethoxy p. amino phenyl arsenic acids, and then reducethem to the tri-valent arsen foxid'. They may also be producedby firstreducing the mother substance to the arsen oxid and treating it w th'ethyl'chlor carbona-t-e- Specification of Letters Patent.

Production of the acids-I produce as sinic acid: 7

30. grams para-ainino-phriyl arseniate' of sodium are dissolved in 300cc. of water con- Patented Dec. 1,1914}.'

-. Application filed April 5, 1913. SerialNo. 759,038.

taining 4 grams-caustic soda. The solution is cooled to about 10 (landtreated with 12 grams of ethyl -chlor carbonate, which is added in smallportions, thoroughly agitating the mixture after'each addition. 'Thefree acid is then separated in crystalline formby the addition of dilutehydrochloric acid. From said carbetho'xyipara. amino pheny'l :arsinicacid I prepare carbethoxy-4- amino-5-nitrophenyl arsinic acid bynitrating with nitric acid.

I produce as follows, carbethoxy 4 5 I 7 diamino-phenyL arsinic acid nncooqm' 60 grams of barium hydroxid are dis-- solved ii -300 cc. warmwater, adding suificient ammonia water until solutionsmells quitestrongly of ammonia. This mixture is then added to'200 cc. of a solutionof 56 grams ferroussulfate. To this are added 5.8

grams, finely powdered,-of said nitro derivative. The mixture is kept ata temperature of about 75 C. and should be wen: stirred.

After 30 minutes the solution is filtered, treated with carbon di-oxid'to remove the sulfuric acid corresponding to the quantity Production ofthe owids.--First. The car.-

bethoxy-para-amino-phenyl-arsen-oxid may be prepared-by the use ofsulfurous acid as follows: 300 cc. of an aqueous solution contaming 29grams of a sol'uble salt (preferably mono-sodium salt) of thecarbethoxy- V para-amino-phenylarsinic acid, and 2 ams i of potassiumiodid, is cooled to and acidified with a, slight excess of sulfuricacid. This solution is treated with sulfurous acid gas, until it issaturated. It is then carefully made alkaline with; an excess ofconcentrated aqua-ammonia, and the arsen oxid is precipitated. Thesubstance fwhich is separatedout is removedby suction and redissolved incold dilute. caustic soda, the

solution filtered and again precipitated with pending 18 grams of dryfinely powdered carbethoxy para-amino-phenyl arsinic acid, or a' saltthereof, in 150 cc. of a non-reacting solvent, such as-acetic ether,achloroformpr carbontetra-chlorid. To this-suspension '12-" gramsphosphorus tri-chlorid are added. gradually (drop. by drop), when a.v'iole'nt- "reaction follows, thelmixture beeomes'warm 1 and thesubstancegoesinto solution; The

solution is, 'fi1tered," the solvent. and the formed phosphorus oicychllorid are removed under reduced pressure. ;The resulting car'bethoxy-para-amino phenyl-arsen dichlorid residue is treated with'diluteIcaustic-soda and stirred untilall has dissolved, when thecorresponding oxid is. precipitatedzwith ammonium chloridsolution ordilute acetic acid.

It may .be' further purified in-the usual manner. Third. Or, the;carbethoxy-paraamino-phenyl-arsen-oxid from para-amino-phenyl-arsen oxidas follows '1 molecule of para-amino-phenyl-arsen-oxid is dissolved inlinolecule of caustic soda and cooled with ice. 'The mixture is treatedwith a slight excess of '1 molecule of ethyl chlor-carbonate, adding itin small portionsfand agitating thoroughly after-each addition.

- lected and purified in the usual; manner.

I The carbethoXyi.5 diamino-phenyl arsen oxid may be prepared in thesame manner as said -carbethoxy-p-amino-phenylsarsenoxid, usingcarbethoxy-4.5 diamino-phenylarsinic acid, with the exception that thefinal reaction with caustic soda is carried out evaporated to dryness in'vacuum,,and the m y be P p 1f .residue extracted with strongalcohol.The

carbethoxy-4.5-diamino-phenyl-arsen o;ld is iobtained by evaporatingtheal'cch under; "reduced pressure; It maybe by redissolvin in alcohol;and co "ntrating 79 the alcoholic solution in vacuuin jandgpre,cipitating with other. I The carbethoxy para aminophenyl-arsen-- oxidhas the, following characteristics: .Itappears in the form of acolorless, odorless powder, very soluble in glacial acetic acid, quitesoluble in alcohol and in hot water, slightly: soluble inwater-"acidulated with ihydro chloric ,aciiL-and only slightly solublein cold water. Itgis insoluble in-chloroform, petroleum ether,carbondisulfid, ether aiid benzol. .When heated in dry form-to about270' it darkens and decomposed with out previouslymelting. ,It dissolvesreadily in dilutesolutions of sodium and. potassium hydroxid, from whichit is precipitated in amorphous form upon the addition of ammoniumchlorid solution, orupon acidulating withacids- However, uponacidulating adilute alkaline solutionof. it with acetic acid, especiallywhen warm, the arsen-oxid slowly separates out crystalline in a formcontainingfiwateri of crystallization, and which, under. microscope,appear like oliydrops."= Itjfdoes' not dissolve in sodium carbonate*solution:- Dilute; alkaline solutions of i't-treatedwithhydrogenfmlfidyield 1 a yellow substance onaeidul'atingzwhieh may be as. anarsensultid compound, in which-the is replaced 10 withone or. morezlltomsf w t Isis s ecific' for iroc 'te a biit is less act ie towiirdtlie cells of the and 4 'mal host than corresponding which the aminogrolpis not by 105 the an et y Ig o p- .i l a The .carbethoxyfi--diaininophenyi arsewxid. PP r h F a at 'as h ly I colored amorphouspowder, 'verysoluble in glacial acetic acid, qtlite' soluble -mialcol 1 bl I10 andslightly in wateri ;It,1s very solublem aeidulated water formingsoluhlesalts. It

dissolves very readily in alkali'mi;

particularly in caustic, which it [cultly preeipitateds It Wasnot to 115a. definite melting :Lflt'n preceding. 01nd it, is ;.:'generally theordinaryforganicsolvent$ specific for spirochsete and tryparios oxnes.

I TheLmthod bfJar-eating hog cholera wi h .120

the fore oin :'-roducts,l*respectively, is to suspendgaboit 02 grams oi,the product in some neutralmedium, such as oliveoll, and inject thissuspension 'hypodermically and intermuscularly into the hog.- ,Onenjection of this suspension into-Ian animal appears to be sufiicient toeffect acomplete cure, and it also appears toact as a prophylacticagainst such infection. a

I believe that I am the first .to discoverof curing that disease.

that an arsenic compound may be a specific for hog cholera, andoriginate this method Although my new products are particularlysuccessful in treating hog cholera, they are also specifics for otherdiseases.

What I claim and desire to secure by Letters Patent of the United,States is:

1. As a new specific an aromatic amino arsenic com ound in which anamino group is combine with at least one carbethoxy group.

2. As a new specific an aromatic amino arsenic compound containing morethan one amino group, in which an amino group is combined with at leastone carbethoxy group.

3. As a new specific an aromatic amino arsenic compound containing a,4-carbethoxyamino group and a 5-amino cup.

4. As a new specific an aromatic amino arsenic compound, in which onehydrogen only of an amino group is replaced by a caroethoxy radical.

5. The process of producing an arsenic 35 compound which consists intreating an amino-phenyl-arsinic compound with a carbethoxy compound.

6. The process'of producing an arsenic compound which consists in tree.an- 34;

amino-.phenyl-arsenic compound w1 a. carbethoxy compound, then mtratingand then reducing the nitro group to the ammo form.

In testimony whereof I have hereunto 35 W. W. Frsmm, O. G. Jorm.

